Abstract

Rationale

Compulsive cocaine use is a key feature of cocaine addiction and understanding the factors that promote the development of such a behavior will provide important insights into the mechanism of cocaine addiction and is essential for the clinical management of the disorder.

Objectives

This study aimed to determine how the preexisting compulsive reward-seeking behavior is related to the development of compulsive cocaine-seeking behavior in male and female rats and the potential impact of the reward value and estrous cycle on such behaviors.

Methods

Adult male and female Wistar rats were first trained to self-administer sucrose pellets under a chained schedule, and then, the intensity-response effects of footshock punishment on sucrose SA reinforced by different values of sucrose were measured. Subsequently, the same rats went on to self-administer intravenous cocaine and the punishment intensity-response effects on cocaine SA reinforced by different doses of cocaine were similarly determined. For the female rats, the measurements were made during different phases of the estrous cycle.

Results

The rats showed a wide range of levels of the compulsive behaviors despite the similar training history. Surprisingly, the compulsive sucrose-seeking behavior did not predict the compulsive cocaine-seeking behavior in either sex. Increasing cocaine dose significantly increased the compulsive cocaine-seeking behavior in the female but not male rats. Estrous cycle did not have impact on the compulsive behaviors.

Conclusion

Preexisting differences in compulsive sucrose-seeking behavior do not predict compulsive cocaine-seeking behavior. Compulsive cocaine-seeking behavior is influenced by cocaine dose but not estrous cycle in the female rats.

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Acknowledgements

The project was supported by Grant Number DA034776 (WLS) from the National Institute on Drug Abuse and its contents are solely the responsibility of the authors and do not necessarily represent the official views of NIDA or NIH. All procedures followed the National Institute of Health Guidelines for the Care and Use of Laboratory Animals. There is no conflict of interest in relation to this article.